The proposals in this project represent direct extensions of our research that for a number of years has sought to define the spectrum of disease which results from acquiring CMV infection in early life (intrauterine and perinatal infection). Because of its striking chronicity when acquired by the fetus and young infant, CMV infection has a potential for producing not only severe acute multi-organ system disease but also a wide range (profound and subtle) of central nervous system and perceptual defects, which conceivably could be progressive for a number of years. Our current proposal is focused on application of state of the art techniques to increasing our understanding of the evolution of CNS disease in congenital CMV infection. We will refine our knowledge of the frequency, range and determinants of neurocognitive deficits through longitudinal multidisciplinary studies in well defined patient populations. We will also attempt to identify CMV infection of the CNS in early infancy using virologic, immunologic and sophisticated imaging techniques. Early identification of CNS involvement could represent an important advance, essential for providing an accurate prognosis, detecting progressive CNS disease and perhaps for identifying patients who could potentially benefit from antiviral therapy.